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IRT-1, a novel interferon-gamma-responsive transcript encoding a growth-suppressing basic leucine zipper protein

M V Autieri1, N Agrawal

  • 1Department of Molecular Biology, Deborah Heart and Lung Research Institute, Browns Mills, New Jersey 08015, USA.

The Journal of Biological Chemistry
|June 17, 1998
PubMed
Summary

A novel Interferon-gamma (IFN-gamma) inducible transcript, IRT-1, is identified in vascular smooth muscle cells (VSMCs). IRT-1 protein overexpression inhibits VSMC proliferation, suggesting its role in vascular proliferative diseases.

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Area of Science:

  • Molecular biology
  • Cell biology
  • Cardiovascular research

Background:

  • Interferon-gamma (IFN-gamma) inhibits vascular smooth muscle cell (VSMC) proliferation and reduces arterial restenosis.
  • Understanding IFN-gamma-specific transcripts in VSMCs is crucial for discerning mechanisms of vascular proliferative diseases.

Purpose of the Study:

  • To identify and characterize novel IFN-gamma-inducible mRNA transcripts in VSMCs.
  • To investigate the role of a newly identified transcript, IRT-1, in vascular cell proliferation and disease.

Main Methods:

  • Quantitative analysis of mRNA expression in human VSMCs and rat carotid arteries.
  • cDNA sequencing and protein domain analysis of IRT-1.
  • Overexpression studies of IRT-1 protein in VSMCs.

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Main Results:

  • A novel mRNA transcript, IRT-1, was identified, constitutively expressed in some human tissues but induced >200-fold in VSMCs by IFN-gamma.
  • IRT-1 mRNA expression was also observed in balloon-injured rat carotid arteries.
  • The IRT-1 transcript encodes a protein with a leucine zipper motif and nuclear localization sequence.
  • Overexpression of IRT-1 protein in VSMCs reduced their proliferative capacity and altered morphology.

Conclusions:

  • IRT-1 is an IFN-gamma-inducible factor expressed in VSMCs.
  • IRT-1 may play a regulatory role in the progression of vascular proliferative diseases.